Experimental physical methods and theories--then and now.

INTRODUCTION: A first evaluation of fundamental research into the physics and physiology of Ultra high dilutions (UHDs) was conducted by the author in 1994(1). In this paper we revisit methods and theories from back then and follow their paths through their evolution and contribution to new knowledge in UHD research since then. METHOD: Physical methods and theories discusses in our anthology on UHD in 1994(1) form the basis for tracing ideas and findings along their path of further development and impact on new knowledge in UHD. RESULTS: Experimental approaches to probe physical changes in homeopathic preparations have become more sophisticated over past two decades, so did the desire to report results to a scientific standard that is on par with those in specialist literature. The same cannot be said about underlying supporting theoretical models and simulations. CONCLUSION: Grant challenges in science often take a more targeted and more concerted approach to formulate a research question and then look for answers. A concerted effort to focus on one hypothesized physical aspect of a well-defined homeopathic preparation may help aligning experimental methods with theoretical models and, in doing so, help to gain a deeper understanding of the whole body of insights and data produced.

Publications on experimental physical methods to investigate ultra high dilutions--an assessment on quality.

INTRODUCTION: Our first evaluation of fundamental research into the physics and physiology of Ultra High Dilution (UHD) was conducted in 1994. Since then, in 2003, Becker-Witt et al. conducted a more systematic evaluation of the literature and established the Score for Assessment of Physical Experiments on Homeopathy (SAPEH). While this evaluation focused on experimental methodologies, Stock-Schröer et al., in 2009, formulated a detailed guideline for authors on Reporting Experiments in Homeopathic Basic research (REHBaR) to promote a high standard in research as well as in its communication in scientific literature. METHOD: In this paper, we evaluate publications on basic research into the physics of UHD since the decade following the presentation of the SAPEH score (2004-2014), and present the state of progress in this field. RESULTS: Fundamental research into the physics of UHD has been reported at a steady rate over the past 60 years. Reported research of high quality as per SAPEH scoring appears to be still the exception rather than standard. CONCLUSION: Considering the importance of a fundamental understanding of what makes a UHD preparation, results of this study suggest that it may be beneficial to this field of fundamental research if grant challenges are approached in strategic way similar to other grant challenges in science.

Geographical and temporal distribution of basic research experiments in homeopathy.

The database HomBRex (Homeopathy Basic Research experiments) was established in 2002 to provide an overview of the basic research already done on homeopathy (http://www.carstens-stiftung.de/hombrex). By this means, it facilitates the exploration of the Similia Principle and the working mechanism of homeopathy. Since 2002, the total number of experiments listed has almost doubled. The current review reports the history of basic research in homeopathy as evidenced by publication dates and origin of publications. In July 2013, the database held 1868 entries. Most publications were reported from France (n = 267), followed by Germany (n = 246) and India (n = 237). In the last ten years, the number of publications from Brazil dramatically increased from n = 13 (before 2004) to n = 164 (compared to n = 251 published in France before 2004, and n = 16 between 2004 and 2013). The oldest database entry was from Germany (1832).

La solidez de la investigación homeopática fundamental / The strength of fundamental homeopathic research

La investigación fundamental en homeopatía ha avanzado considerablemente en los últimos 20 años: desde estudios exploratorios con animales y plantas hasta la caracterización de los efectos sistémicos de los medicamentos homeopáticos y estudios in vitro con sistemas celulares aislados para evaluar los cambios en los mecanismos de adaptación celular y señalización intracelular frente a tratamientos homeopáticos variables. El número de artículos publicados a lo largo del tiempo ha permitido realizar varias revisiones sistemáticas. Recientemente, la demostración de que los medicamentos homeopáticos podrían modificar las funciones celulares a través de mecanismos epigenéticos (metilación y desmetilación de ADN) preparó el camino para un campo de investigación completamente nuevo. En paralelo, el descubrimiento de las nanopartículas y propiedades físicas específicas de las diluciones homeopáticas ha arrojado luz hacia un campo antes poco conocido, dado que se consideraba que las diluciones homeopáticas no consistían más que de agua. Así las cosas, los retos para el futuro conciernen a la demostración, o no, de la interrelación entre ambos fenómenos.

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

As evidências a favor da homeopatia e as ciências básicas / Evidence for the homeopathic principles in the basic sciences

Como toda área da medicina, a homeopatia é tanto arte quanto ciência. Enquanto a pesquisa clínica visa responder "se" e "quando" os medicamentos homeopáticos são capazes de restabelecer a saúde, as ciências básicas ­ biologia, imunologia, patologia, química, física e farmacologia ­ geram diversas hipóteses plausíveis para dar conta do "como" agem os medicamentos diluídos e dinamizados (MDD) em modelos experimentais rigorosos. A ação farmacodinâmica dos MDD depende do fornecimento de pequenas quantidades de informação a alvos orgânicos específicos, de maneira a restabelecer um comportamento mais próximo do estado ótimo de saúde. Alguns mecanismos de ação dos MDD podem ser identificados em estudos de laboratório. O princípio de semelhança terapêutica pode ser observado em modelos horméticos, de acordo com a lei de Arndt-Schutz, nos quais a inversão de efeitos é obtida modificando a dose. Igualmente, em modelos de tipo Wilder, são comparados organismos estressados e normais. No entanto, a hormese utiliza medicamentos em pequenas doses, enquanto na homeopatia são utilizados medicamentos em diluições além da faixa material, que além disso precisam ser agitados. O presente artigo dedica atenção especial ao modelo de degranulação dos basófilos, que em 2018 completa 30 anos de desenvolvimento. Igualmente são abordados os trabalhos do nosso grupo, na Universidade de Verona, Itália. (AU)

As any other medical field, homeopathy is both art and science. Clinical research seeks to answer the questions on "whether" and "when" homeopathic medicines are able to restore health. In turn, the fundamental sciences­biology, immunology, pathology, chemistry, physics and pharmacology­generate plausible hypothesis to explain "how" serially diluted and agitated medicines (SDAM) act in rigorous experimental models. The pharmacodynamic action of SDAM depends on the supply of subtle information input to specific body targets in order to restore a pattern of behavior closer to optimal health. Some mechanisms of action of SDAM might be identified in laboratory studies. The therapeutic similarity principle might be observed in hormesis models, according to Arndt-Schutz's law, in which effect inversion is obtain through changes of dose. Wilder-like models compared stressed and healthy subjects. However, hormesis uses drugs in small doses, while homeopathy uses medicines diluted beyond the scope of matter, which in addition must be agitated. In the present article I paid special attention to the basophil degranulation, as in 2018 it completes its 30th anniversary. I also summarized the results of our work at University of Verona, Italy. (AU)

The soundness of homeopathic fundamental research

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

The soundness of homeopathic fundamental research

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.(AU)

A solidez da pesquisa básica em homeopatia / The soundness of homeopathic fundamental research

A pesquisa básica em homeopatia evoluiu muito nos últimos 20 anos. Desde estudos exploratórios realizados em animais e plantas para a caracterização dos efeitos sistêmicos dos medicamentos homeopáticos até estudos realizados in vitro, com sistemas celulares isolados, para avaliar mudanças nos mecanismos de adaptação celulares e nos processos de sinalização intracelular frente a tratamentos homeopáticos diversos. O volume de artigos acumulados ao longo dos anos permitiu a elaboração de várias revisões sistemáticas sobre o tema. Recentemente, a demonstração de que medicamentos homeopáticos podem modificar as funções celulares por mecanismosepigenéticos (metilação e desmetilação do DNA) abriu espaço para uma nova frente de pesquisas. Em paralelo, a partir de 2010, a descoberta da existência de nanopartículas e de propriedades físicas da água específicas nas preparações homeopáticas também jogou luz num campo até então pouco conhecido, em que se acreditava não existir nada além de água. Os desafios para o futuro se concentram, então, na demonstração,ou não, de que ambos os processos se inter-relacionam.(AU)

A solidez da pesquisa básica em homeopatia / The solidity of basic research in homeopathy

A pesquisa básica em homeopatia evoluiu muito nos últimos 20 anos. Desde estudos exploratórios realizados em animais e plantas para a caracterização dos efeitos sistêmicos dos medicamentos homeopáticos até estudos realizados in vitro, com sistemas celulares isolados, para avaliar mudanças nos mecanismos de adaptação celulares e nos processos de sinalização intracelular frente a tratamentos homeopáticos diversos. O volume de artigos acumulados ao longo dos anos permitiu a elaboração de várias revisões sistemáticas sobre o tema. Recentemente, a demonstração de que medicamentos homeopáticos podem modificar as funções celulares por mecanismosepigenéticos (metilação e desmetilação do DNA) abriu espaço para uma nova frente de pesquisas. Em paralelo, a partir de 2010, a descoberta da existência de nanopartículas e de propriedades físicas da água específicas nas preparações homeopáticas também jogou luz num campo até então pouco conhecido, em que se acreditava não existir nada além de água. Os desafios para o futuro se concentram, então, na demonstração,ou não, de que ambos os processos se inter-relacionam. (AU)

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of published articles amassed over time allowed for several systematic reviews on this subject. Recently, the demonstration the homeopathic medicines might alter cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties in the homeopathic dilutions brought light into a field poorly known before, as it was believe that homeopathic dilutions consist in nothing but water. Thus being, the challenges forthe future concern the demonstration, or not, of the interrelationship between both phenomena. (AU)

Wheat germination and highly diluted agitated gibberellic acid (10-30) ? a multi researcher study / Germinação do trigo e ácido giberélico em alta diluição (10-30) e agitado ? um estudo multicêntrico / Germinación de trigo y ácido giberélico en alta dilución (10-30) y agitado ? estudio multicéntrico

Grains of winter wheat (Triticum aestivum L., Capo variety) were observed under the influence of highly diluted gibberellic acid (10-30) prepared by stepwise dilution and agitation according to a protocol derived from homeopathy (?G30x?). Adequate control was used (water prepared according to the homeopathic protocol ?W30x? and/or untreated water ?W0?). Two sets of multicenter experiments were performed, 4 in 2009-2010 and 4 in 2011, involving altogether 6 researchers, 6 laboratories and 4,000 grains per treatment group. Data were found to be homogeneous within the control groups as well as within the verum groups. When the 2009-2010 experiments were pooled, mean germination rates after 24 hours were (85.9 + 2.6) for the control group and (82.1 + 5.7) for G30x (mean + SD at the level of experiments in %) (N = 2,000 per group). Verum germination rate was 4.4% lower than (i.e. equal to 96.6% of) (4.4 + 96.6 = 101) the control germination rate (100%). The difference is statistically significant (p < 0.001) and the effect size (d) is large (> 0.8). Observations at other points in time between 0 and 40 hours of germination yielded similar results. Practically no difference was found between W30x and W0 groups (p > 0.05). When the 2011 experiments were pooled, the mean germination rates after 24 hours were (73 + 12) for the control group and (73 + 14) for G30x (N = 2,000 per group), i.e. there was practically no difference between the groups (p > 0.05). We interpret the data from 2009-2010 on wheat germination within 40 hours as being in line with our previous findings on wheat stalk growth after one week, i.e. as confirmation that gibberellic acid 30x can influence, i.e. slow down, wheat development. Various possible reasons for the absence of any difference between groups in the 2011 experiments, including seasonal variance, are discussed and it is suggested to perform wheat germination experiments in the very beginning of autumn season only.

Grãos de trigo comum (Triticum sativum L., variedade Capo) foram observados sob a influência de uma alta diluição de ácido giberélico (10-30) preparada através de diluição e agitação seriadas seguindo um protocolo derivado da homeopatia (G30x). Foram utilizados controles adequados (água preparada segundo o protocolo homeopático - W30x - e/ou água sem tratamento - W0 -). Foram realizadas duas séries de experimentos multicêntricos, 4 em 2009-2010 e 4 em 2011, incluindo 6 pesquisadores, 6 laboratórios, e 4.000 grãos em cada grupo de tratamento. Os dados foram homogêneos dentro dos grupos controle e verum. Na análise combinada dos experimentos de 2009-2010, as taxas médias de germinação em 24 h foram (85,9 + 2,6) no grupo controle e (82,1 + 5,7) no grupo G30x (média + DP no nível dos experimentos em %, N = 2.000 por grupo). A taxa de germinação de verum foi 4,4% menor (96,6% de 4,4 + 96,6 = 101) que a do controle (100%). Essa diferença é estatisticamente significativa (p < 0,001) e o tamanho do efeito (d) é grande (> 0,8). Observações realizadas em outros momentos entre 0 e 40 horas de germinação constaram resultados similares. Praticamente, não foi achada diferença entre os grupos W30x e W0 (p > 0,05). Na análise combinada dos experimentos de 2011, as taxas médias de germinação em 24 h foram (73 + 12) no grupo controle e (73 + 14) no grupo G30x (N = 2.000 por grupo), ou seja, praticamente não houve diferença entre os grupos (p > 0,05). Consideramos que os dados de 2009-2010 sobre a germinação do trigo em até 40 h concordam com nos achados prévios no crescimento do caule de trigo em uma semana, ou seja, confirmam que ácido giberélico 30x pode influenciar, isto é, tornar mais lento, o desenvolvimento do trigo. São discutidos vários motivos para a ausência de toda diferença entre os grupos nos experimentos conduzidos em 2011, incluindo variações sazonais, e sugere-se que os experimentos com germinação de trigo sejam realizados exclusivamente no começo do outono.

Wheat germination and highly diluted agitated gibberellic acid (10-30) ? a multi researcher study / Germinação do trigo e ácido giberélico em alta diluição (10-30) e agitado ? um estudo multicêntrico / Germinación de trigo y ácido giberélico en alta dilución (10-30) y agitado ? estudio multicéntrico

Grains of winter wheat (Triticum aestivum L., Capo variety) were observed under the influence of highly diluted gibberellic acid (10-30) prepared by stepwise dilution and agitation according to a protocol derived from homeopathy (?G30x?). Adequate control was used (water prepared according to the homeopathic protocol ?W30x? and/or untreated water ?W0?). Two sets of multicenter experiments were performed, 4 in 2009-2010 and 4 in 2011, involving altogether 6 researchers, 6 laboratories and 4,000 grains per treatment group. Data were found to be homogeneous within the control groups as well as within the verum groups. When the 2009-2010 experiments were pooled, mean germination rates after 24 hours were (85.9 + 2.6) for the control group and (82.1 + 5.7) for G30x (mean + SD at the level of experiments in %) (N = 2,000 per group). Verum germination rate was 4.4% lower than (i.e. equal to 96.6% of) (4.4 + 96.6 = 101) the control germination rate (100%). The difference is statistically significant (p < 0.001) and the effect size (d) is large (> 0.8). Observations at other points in time between 0 and 40 hours of germination yielded similar results. Practically no difference was found between W30x and W0 groups (p > 0.05). When the 2011 experiments were pooled, the mean germination rates after 24 hours were (73 + 12) for the control group and (73 + 14) for G30x (N = 2,000 per group), i.e. there was practically no difference between the groups (p > 0.05). We interpret the data from 2009-2010 on wheat germination within 40 hours as being in line with our previous findings on wheat stalk growth after one week, i.e. as confirmation that gibberellic acid 30x can influence, i.e. slow down, wheat development. Various possible reasons for the absence of any difference between groups in the 2011 experiments, including seasonal variance, are discussed and it is suggested to perform wheat germination experiments in the very beginning of autumn season only.(AU)

Grãos de trigo comum (Triticum sativum L., variedade Capo) foram observados sob a influência de uma alta diluição de ácido giberélico (10-30) preparada através de diluição e agitação seriadas seguindo um protocolo derivado da homeopatia (G30x). Foram utilizados controles adequados (água preparada segundo o protocolo homeopático - W30x - e/ou água sem tratamento - W0 -). Foram realizadas duas séries de experimentos multicêntricos, 4 em 2009-2010 e 4 em 2011, incluindo 6 pesquisadores, 6 laboratórios, e 4.000 grãos em cada grupo de tratamento. Os dados foram homogêneos dentro dos grupos controle e verum. Na análise combinada dos experimentos de 2009-2010, as taxas médias de germinação em 24 h foram (85,9 + 2,6) no grupo controle e (82,1 + 5,7) no grupo G30x (média + DP no nível dos experimentos em %, N = 2.000 por grupo). A taxa de germinação de verum foi 4,4% menor (96,6% de 4,4 + 96,6 = 101) que a do controle (100%). Essa diferença é estatisticamente significativa (p < 0,001) e o tamanho do efeito (d) é grande (> 0,8). Observações realizadas em outros momentos entre 0 e 40 horas de germinação constaram resultados similares. Praticamente, não foi achada diferença entre os grupos W30x e W0 (p > 0,05). Na análise combinada dos experimentos de 2011, as taxas médias de germinação em 24 h foram (73 + 12) no grupo controle e (73 + 14) no grupo G30x (N = 2.000 por grupo), ou seja, praticamente não houve diferença entre os grupos (p > 0,05). Consideramos que os dados de 2009-2010 sobre a germinação do trigo em até 40 h concordam com nos achados prévios no crescimento do caule de trigo em uma semana, ou seja, confirmam que ácido giberélico 30x pode influenciar, isto é, tornar mais lento, o desenvolvimento do trigo. São discutidos vários motivos para a ausência de toda diferença entre os grupos nos experimentos conduzidos em 2011, incluindo variações sazonais, e sugere-se que os experimentos com germinação de trigo sejam realizados exclusivamente no começo do outono.(AU)